title: Lipid transfer protein I facilitated transfer of cyclosporine from low- to high-density lipoproteins is only partially dependent on its cholesteryl ester transfer activity.
abstract: The purpose of this study was to determine if lipid transfer protein (LTP I) regulates the plasma lipoprotein distribution of cyclosporine (CSA). Experimental strategies that involved the supplementation and inhibition of LTP I were used to test these hypotheses. Incubation of CSA with human plasma supplemented with exogenous LTP I resulted in a significantly greater percentage of CSA recovered in the high-density lipoprotein (HDL)/lipoprotein deficient plasma (LPDP) fraction than in the low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL) fraction compared to plasma which had no exogenous LTP I added. Incubation of radiolabeled cholesteryl ester (CE) or CSA-enriched HDL or LDL in T150 buffer supplemented with LTP I resulted in a significantly greater percentage of CE than CSA being transferred from HDL to LDL and LDL to HDL. However, the percent transfer from LDL to HDL was significantly lower for CE than CSA when these particles were incubated in LPDP that contained endogenous LTP I. The percent transfer of CE from HDL to LDL and LDL to HDL was significantly decreased in the presence of TP2, a monoclonal antibody directed against LTP I, compared to controls. The percent transfer of CSA from LDL to HDL was significantly decreased in the presence of TP2. However, the percent transfer of CSA from HDL to LDL in the presence of TP2 was not significantly different compared to controls. These findings suggest that the transfer of CSA between HDL and LDL is only partially facilitated through LTP I CE transfer activity.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: K M
authors.initials: KM
authors.lastname: Wasan
authors.forename: M
authors.initials: M
authors.lastname: Ramaswamy
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: P H
authors.initials: PH
authors.lastname: Pritchard
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood; D016572:Cyclosporine / Q000097:blood*; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016572:Cyclosporine